Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10151)
Regulator Name Lysine-specific demethylase 5C (KDM5C)
Synonyms
Histone demethylase JARID1C; Jumonji/ARID domain-containing protein 1C
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Gene Name KDM5C
Gene ID 8242
Regulator Type Protein coding
Uniprot ID P41229
Sequence
MEPGSDDFLPPPECPVFEPSWAEFRDPLGYIAKIRPIAEKSGICKIRPPADWQPPFAVEV
DNFRFTPRIQRLNELEAQTRVKLNYLDQIAKFWEIQGSSLKIPNVERRILDLYSLSKIVV
EEGGYEAICKDRRWARVAQRLNYPPGKNIGSLLRSHYERIVYPYEMYQSGANLVQCNTRP
FDNEEKDKEYKPHSIPLRQSVQPSKFNSYGRRAKRLQPDPEPTEEDIEKNPELKKLQIYG
AGPKMMGLGLMAKDKTLRKKDKEGPECPPTVVVKEELGGDVKVESTSPKTFLESKEELSH
SPEPCTKMTMRLRRNHSNAQFIESYVCRMCSRGDEDDKLLLCDGCDDNYHIFCLLPPLPE
IPKGVWRCPKCVMAECKRPPEAFGFEQATREYTLQSFGEMADSFKADYFNMPVHMVPTEL
VEKEFWRLVNSIEEDVTVEYGADIHSKEFGSGFPVSDSKRHLTPEEEEYATSGWNLNVMP
VLEQSVLCHINADISGMKVPWLYVGMVFSAFCWHIEDHWSYSINYLHWGEPKTWYGVPSL
AAEHLEEVMKKLTPELFDSQPDLLHQLVTLMNPNTLMSHGVPVVRTNQCAGEFVITFPRA
YHSGFNQGYNFAEAVNFCTADWLPAGRQCIEHYRRLRRYCVFSHEELICKMAACPEKLDL
NLAAAVHKEMFIMVQEERRLRKALLEKGITEAEREAFELLPDDERQCIKCKTTCFLSALA
CYDCPDGLVCLSHINDLCKCSSSRQYLRYRYTLDELPAMLHKLKVRAESFDTWANKVRVA
LEVEDGRKRSLEELRALESEARERRFPNSELLQQLKNCLSEAEACVSRALGLVSGQEAGP
HRVAGLQMTLTELRAFLDQMNNLPCAMHQIGDVKGVLEQVEAYQAEAREALASLPSSPGL
LQSLLERGRQLGVEVPEAQQLQRQVEQARWLDEVKRTLAPSARRGTLAVMRGLLVAGASV
APSPAVDKAQAELQELLTIAERWEEKAHLCLEARQKHPPATLEAIIREAENIPVHLPNIQ
ALKEALAKARAWIADVDEIQNGDHYPCLDDLEGLVAVGRDLPVGLEELRQLELQVLTAHS
WREKASKTFLKKNSCYTLLEVLCPCADAGSDSTKRSRWMEKELGLYKSDTELLGLSAQDL
RDPGSVIVAFKEGEQKEKEGILQLRRTNSAKPSPLASSSTASSTTSICVCGQVLAGAGAL
QCDLCQDWFHGRCVSVPRLLSSPRPNPTSSPLLAWWEWDTKFLCPLCMRSRRPRLETILA
LLVALQRLPVRLPEGEALQCLTERAISWQGRARQALASEDVTALLGRLAELRQRLQAEPR
PEEPPNYPAAPASDPLREGSGKDMPKVQGLLENGDSVTSPEKVAPEEGSGKRDLELLSSL
LPQLTGPVLELPEATRAPLEELMMEGDLLEVTLDENHSIWQLLQAGQPPDLERIRTLLEL
EKAERHGSRARGRALERRRRRKVDRGGEGDDPAREELEPKRVRSSGPEAEEVQEEEELEE
ETGGEGPPAPIPTTGSPSTQENQNGLEPAEGTTSGPSAPFSTLTPRLHLPCPQQPPQQQL

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Family JARID1 histone demethylase family
Function
Histone demethylase that specifically demethylates 'Lys-4' of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-9', H3 'Lys- 27', H3 'Lys-36', H3 'Lys-79' or H4 'Lys-20'. Demethylates trimethylated and dimethylated but not monomethylated H3 'Lys-4'. Participates in transcriptional repression of neuronal genes by recruiting histone deacetylases and REST at neuron-restrictive silencer elements. Represses the CLOCK-BMAL1 heterodimer-mediated transcriptional activation of the core clock component PER2.

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HGNC ID
HGNC:11114
KEGG ID hsa:8242
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
KDM5C can regulate the following target(s), and cause disease/drug response(s). You can browse detail information of target(s) or disease/drug response(s).
Browse Target
Browse Disease
Unspecific Target [Unspecific Target]
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Responsed Disease Hereditary Leiomyomatosis ICD-11: 2C90
 Disease Info 
Pathway Response Pentose phosphate pathway hsa00030
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 RCC4 cells Clear cell renal cell carcinoma Homo sapiens CVCL_0498
ACHN cells Papillary renal cell carcinoma Homo sapiens CVCL_1067
786-O cells Renal cell carcinoma Homo sapiens CVCL_1051
769-P cells Renal cell carcinom Homo sapiens CVCL_1050
Caki-1 cells Clear cell renal cell carcinoma Homo sapiens CVCL_0234
A-498 cells Renal cell carcinoma Homo sapiens CVCL_1056
HK-2 cells Normal Homo sapiens CVCL_0302
In Vivo Model
For the xenograft of RCC4 cells, four-week-old female NOD. At 6th week, mice were injected with 100 uL of stable RCC4-EV or RCC4-KDM5C cells suspended in Matrigel Basement Membrane Matrix (Corning, 356234) at a population of 1 x 107 cells into the left or right dorsal flank subcutaneously after alcohol sterilization of injection site skin surface. On day 7 after injection, the mice were randomly divided into 2 groups and treated with Liproxstatin-1 (10 mg/kg, MCE HY-12726) or vehicle control (1% DMSO in PBS) each other day by i.p. injection.

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Response regulation Poor survival rates of clear cell renal cell carcinoma patients seem to be associated with up-regulation of the pentose phosphate pathway (PPP). KDM5C re-expression suppressed the glucose flux through PPP and re-sensitized cancer cells to ferroptosis. Furthermore, KDM5C deficiency predicted the poor prognosis, and clinically relevant KDM5C mutants failed to suppress glycogen accumulation and promoted ferroptosis as wild type.
Hereditary Leiomyomatosis [ICD-11: 2C90]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Lysine-specific demethylase 5C (KDM5C) Protein coding
 Regulator Info 
Pathway Response Pentose phosphate pathway hsa00030
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 RCC4 cells Clear cell renal cell carcinoma Homo sapiens CVCL_0498
ACHN cells Papillary renal cell carcinoma Homo sapiens CVCL_1067
786-O cells Renal cell carcinoma Homo sapiens CVCL_1051
769-P cells Renal cell carcinom Homo sapiens CVCL_1050
Caki-1 cells Clear cell renal cell carcinoma Homo sapiens CVCL_0234
A-498 cells Renal cell carcinoma Homo sapiens CVCL_1056
HK-2 cells Normal Homo sapiens CVCL_0302
In Vivo Model
For the xenograft of RCC4 cells, four-week-old female NOD. At 6th week, mice were injected with 100 uL of stable RCC4-EV or RCC4-KDM5C cells suspended in Matrigel Basement Membrane Matrix (Corning, 356234) at a population of 1 x 107 cells into the left or right dorsal flank subcutaneously after alcohol sterilization of injection site skin surface. On day 7 after injection, the mice were randomly divided into 2 groups and treated with Liproxstatin-1 (10 mg/kg, MCE HY-12726) or vehicle control (1% DMSO in PBS) each other day by i.p. injection.

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Response regulation Poor survival rates of clear cell renal cell carcinoma patients seem to be associated with up-regulation of the pentose phosphate pathway (PPP). KDM5C re-expression suppressed the glucose flux through PPP and re-sensitized cancer cells to ferroptosis. Furthermore, KDM5C deficiency predicted the poor prognosis, and clinically relevant KDM5C mutants failed to suppress glycogen accumulation and promoted ferroptosis as wild type.
References
Ref 1 Deficiency of the X-inactivation escaping gene KDM5C in clear cell renal cell carcinoma promotes tumorigenicity by reprogramming glycogen metabolism and inhibiting ferroptosis. Theranostics. 2021 Aug 4;11(18):8674-8691. doi: 10.7150/thno.60233. eCollection 2021.